Hemoglobin最新文献

Patients suffering from thalassemia are recipients of routine transfusions leading to hemosiderosis. Taking iron chelating agents is mandatory. Several studies have shown different results regarding the occurrence of kidney complications in thalassemia patients who received iron-chelating agents. In this study, we were looking for kidney complications by examining human NAG urine/serum and NGAL urine/serum in thalassemia community in East Java community. The study was conducted cross-sectionally in the thalassemia community in East Java with a total sample of 91 patients aged 13-48 years. All thalassemia patients filled in demographic data, transfusion routines, duration of taking iron chelating agents, and length of time diagnosed with thalassemia. Laboratory tests included routine blood tests for ferritin, ureum, serum creatinine, human NAG urine or serum, and human NGAL urine or serum. Comparison tests (t-test, Mann-Whitney, and ANOVA, Kruskal-Wallis) were conducted to see if there were significant differences in the levels of human NAG urine and human NGAL urine serum based on age, sex, blood group, duration of transfusion, routine of transfusion, duration of taking iron chelating agents, and types of iron chelating drugs. Multivariate analysis was conducted to see whether some of these categories were related to abnormalities in human NAG urine or serum and human NGAL urine or serum. All 91 patients had normal creatinine values, yet some had abnormal serum NAG. There is a significant difference in urine human NAG and urine human NGAL levels at ages over 23 years (p = 0.05 and p = 0.01). Significant differences in human NGAL serum were also found in working and student patients (p = 0.028). Serum NGAL also differed in those taking deferasirox (p = 0.030) and significantly different human NGAL urine was also found in iron overload status (Ferritin ≥ 1000 ng.ml) (p = 0.006). There is no difference between human NAG urine/serum and human NGAL urine/serum based on sex, body mass index, blood type, hemoglobin less than 10 g/dl, routine transfusion once a month, duration of using iron chelation for more than 10 years, or splenomegaly status (splenomegaly, splenectomy, or no splenomegaly). The multivariate logistic regression results showed that age above 23 was a factor associated with abnormal urine human NAG levels (aOR = 3.79, 95% CI = 1.08-13.28). Students (aOR = 4.89, 95% CI = 1.48-16.16) with ages above 23 years (aOR = 3.69, 95% CI = 1.09-12.43) showed higher risk for an abnormal serum human NGAL levels. Patients with beta-thalassemia major exhibit noticeable tubular damage. Further research is encouraged to determine other factors behind tubular damage in the thalassemia community, particularly in Indonesia.

Hereditary hemoglobinopathies, particularly β-thalassemia, are highly prevalent in Azerbaijan, posing a significant public health challenge. In response, the Azerbaijani government implemented a national prevention program that includes mandatory premarital screening and prenatal diagnosis for at-risk couples, aiming to mitigate the impact of these diseases. This report covers the first five years of the program, beginning in 2015. Among 287 identified at-risk couples, 271 fetal samples were analyzed, revealing that 148 were carriers, 63 were affected, and 60 were unaffected. In nearly all cases, affected pregnancies were terminated. The most common mutations detected were Codon 8 [-AA], IVS-II-1 [G > A], and IVS-I-110 [G > A] in the HBB gene. Since the program's inception, the birth rate of affected children has significantly decreased, making this established approach a valuable model for other regions facing similar challenges with autosomal recessive disorders.

In a previously reported equilibrium study of the reaction of 5,5'-dithiobis(2-nitrobenzoate), DTNB, with various carbonmonoxyhemoglobins over the pH range 5.6 to 9, we obtained contradictory results on the influence of the allosteric effector inositol hexakisphosphate (inositol-P₆) on the DTNB reaction. For this reason, we replaced the carbonmonoxyhemoglobins with oxyhemoglobins and investigated the effect of inositol-P₆ on the equilibrium and kinetics of their reactions with DTNB over the same pH range. We found that there are two sets of oxyhemoglobins: (i) In guinea fowl (major) and in dog oxyhemoglobin, inositol-P₆ decreases both the DTNB affinity and the apparent second-order rate constant of the DTNB reaction; and (ii) in the major and minor goat oxyhemoglobins, inositol-P₆ increases each of these two parameters. The x-ray structure of guinea pig methemoglobin shows that it has the R2 quaternary structure. Inositol-P₆ decreased the DTNB affinity of guinea pig oxyhemoglobin throughout our experimental pH range. On the basis of the guinea pig result, we associate the oxyhemoglobins in set (i) with the R2 quaternary structure and those in set (ii) with the R quaternary structure. We conclude that oxyhemoglobins that do not belong to either of these two sets - those of guinea fowl (minor), horse (major), donkey and human - contain equilibrium mixtures of the R and R2 quaternary structures.

Beta-thalassemia is an inherited disorder prevalent in Thailand and Southeast Asia. Several molecular techniques for identifying β-thalassemia mutations have been reported. Next-generation sequencing (NGS) is a type of effective molecular testing with high throughput and accuracy. Hence, this study aims to evaluate a novel barcode-tagged NGS approach based on a short-read assay. A total of 258 samples with 54 different β-thalassemia genotypes related to 32 mutations were gathered and evaluated. A library was constructed with the BTSeq^TM kit and sequencing was performed on the Illumina NGS machine. The validation results showed 98.45% concordance with conventional genotypes. Less discordant results (1.55%) were limited to insertional mutations and included one case of each of the following: HBB:c.27dupG, HBB:c.85dupC, HBB:c.216dupT, and HBB:c.440_441dupAC. Five single-nucleotide polymorphisms that derived from the NGS results were also analyzed in terms of allele frequency and revealed significant differences between the wild types and other β-genotypes. Furthermore, this paper is the first to describe rare single-nucleotide polymorphisms including IVS II-109 (C/T), IVS II-258 (G/A), IVS II-613 (T-C), and IVS II-806 (G/C). Interestingly, the C allele of IVS II-806 was found to have 100% linkage with two cases of Hb Tak. The haplotype and phylogenetic analysis was also constructed based on variants and revealed three clusters in the Hb variants, which represented their evolution and genetic background. Finally, NGS with the barcode-tagged method has a high throughput, which is suitable for large population screening. Its cost effectiveness and less complicated process promote its application in further works.

Hemoglobin (Hb) Chile, a variant of Hb M, is produced by a point mutation of CTG→ATG on codon 29 (legacy codon 28) of the Hb β locus gene, which results in an amino acid substitution of Leu→Met. It has been identified in two families worldwide and is inherited in an autosomal dominant manner. Here, we report a case of Hb Chile in which a de novo mutation was detected in the proband. A 17-year-old male presented to the outpatient clinic with a pale appearance. There was cyanosis on his lips and fingers. Blood tests indicated the existence of hemolysis, but complete blood counts revealed no anemia. Peripheral arterial oxygen saturation on pulse oximetry was 80% on room air and did not improve with oxygen supplementation. The level of methemoglobin was 15.4%. Targeted next-generation sequencing identified a heterozygous NM_000518.4(HBB):c.85C > A mutation, indicating Hb Chile. The Hb Chile mutation, on the other hand, was not discovered in his parents, implying that it arose as a result of a de novo mutation. This case highlights the necessity of suspecting Hb gene mutations in patients with unexplained chronic methemoglobinemia, even if there is no family history.

Thalassemia is a heterogenous group of hemoglobinopathies; intermediate thalassemia's phenotype can be very variegated due to different genetic matching. Before NGS-era, diagnosis often mismatched with phenotypes, hiding some genetic findings that nowadays could completely explain clinical presentation. In this report, we emphasize the importance of reevaluating genetic testing to achieve a correct diagnosis in case of phenotype mismatch thalassemia. Starting from a suspect of δ/β thalassemia heterozygosity, reevaluating revealed heterozygosity for α-gene triplication combined to δ and β heterozygosity, a new finding that completely suited patient's clinical manifestation. This case provided the opportunity to underline that an extended study on total globin genes is essential for correct diagnosis of thalassemia, especially when clinical onset phenotypes are more divisive and questionable at a first clinical work-up.

Sickle cell disease (SCD) is a prevalent inherited blood disorder arising from a single point mutation that results in substitution of valine with glutamic acid in the Beta hemoglobin chain, making red blood cells assume a banana shape under low oxygen state. It is most prevalent in sub-Saharan Africa, affecting approximately 2% of the population in Mali. This study aimed to evaluate the iron status and associated hematological parameters in SCD patients at steady state in an environment with a high prevalence of iron deficiency. A cross-sectional study was conducted at the Center de Recherche et de Lutte contre la Drépanocytose (CRLD) in Bamako, Mali, involving 757 SCD patients aged 10 to 29 years. Iron deficiency was defined as serum ferritin < 20 ng/mL, while iron overload was associated with serum ferritin > 500 ng/mL. The study population consisted of 171 (22.6%) hemolytic phenotypes (SS and Sβ⁰) and 586 (77.4%) viscous phenotypes (SC and Sβ⁺). Iron deficiency was found in 19 SCD patients (2.5%), with a higher prevalence in the SC phenotype (68.4%). All iron-deficient subjects exhibited microcytosis (MCV < 80 fL) and hypochromia (MCH < 26 pg). Hemoglobin levels < 12 g/dL were observed only in homozygous SCD patients. Low reticulocyte counts were noted in iron-deficient subjects with SC and Sβ+ phenotypes, but not in iron-deficient SS subjects. Serum C-reactive protein (CRP) was normal (< 10 mg/L) in all iron-deficient subjects, excluding iron deficiency due to chronic inflammation. Iron deficiency was observed among 2.5% of the study population, with a predominant occurrence among those with SC phenotype. All iron deficient subjects had microcytosis and hypochromia. Hemoglobin levels below 12 g/dL were only found in homozygous SCD patients. Additionally, low reticulocyte counts were noted in iron deficient patients with SC and Sβ+ phenotypes, though not in those with the SS phenotype. These findings contribute to the understanding of iron status in SCD patients in an African context and highlights the importance of monitoring iron levels in these population to prevent complications associated with iron deficiency or overload.

PIEZO1 (piezo-type mechanosensitive ion channel component 1) is a mechanosensitive ion channel protein. Gain-of-function variants in the PIEZO1 gene are known to cause dehydrated hereditary stomatocytosis (DHS) also termed hereditary xerocytosis. This is a rare autosomal dominant condition characterized by variable-degree anemia with a tendency toward hemolysis, erythrocyte dehydration and iron overload. While the diagnostic workflow for DHS is well-established, diagnosis is often delayed due to overlapping clinical features with other hemolytic anemias and the pleiotropic effects of PIEZO1 variants. We describe the case of a Greek patient with a compensating hemolysis since birth. DHS diagnosis was established only after a prolonged history of repeated investigations spanning from his early life to 70 years of age, when a conclusive testing was achieved.

We report a novel large α-globin gene cluster deletion in a Chinese family from the Guangxi Zhuang Autonomous Regionfor the first time. The proband was a 20-year-old male who presented with microcytic hypochromatosis. Routine genetic analysis showed none of the common mutations in theα-globin and β-globin genes. Multiplex ligation-dependent probe amplification (MLPA) of the α-globin chain revealed there was a large deletion, which removed the entire HBA2 and HBA1 genes, HBQ gene, HBZ gene, and major regulatory element HS-40, eliminating more than 134 kb from the α-globin chain. Subsequently, pedigree analysis revealed that the proband inherited the novel deletion from his father. By consultation of literature and databases, it was confirmed as a hitherto undescribed chain deletion and named Laibin deletion (-^LB) for the origin of the proband.